The ultimate goal of the experiments proposed here is a better understanding of the molecular mechanisms by which the v-erb B oncogene of avian erythroblastosis virus transforms host cells to an oncogenic state. Functional domains within the v-erb B gene product will be identified and the specific roles these different domains play in establishing the transformed phenotype will be determined by use of site-directed mutagenesis and recombinant DNA techniques. Specific aspects of three broad questions will be addressed: A. What specific features of the v-erb B protein are responsible for the target cell specificity of this oncogene? A genetic dissection of this phenomenon is proposed. B. Is the v-erb polypeptide subject to the same regulatory processes operative on its normal cell progenitor, the EGF- receptor (c-erb B protein)? This question seeks to better understand the molecular and biochemical basis behind the "activation" of the mitogenic EGF-receptor into the oncogenic v- erb B protein. C. What is the site of action of the v-erb B protein in the transformed cell? This question has important implications for identifying the location, and the nature, of the host cell "target" polypeptides which must interact with the v-erb B protein to mediate oncogenic transformation. These experiments will provide novel information on the mechanism of action of v-erb B in viral-mediated oncogenesis. In addition, due to the close inter-relatedness between the v-erb B protein and the host cell EGF-receptor, these experiments will help in understanding the relationship between processes regulating growth and proliferation in normal and neoplastic cells.